Research
Print page Print page
Switch language
The Capital Region of Denmark - a part of Copenhagen University Hospital
Published

Next-generation sequencing of 100 candidate genes in young victims of suspected sudden cardiac death with structural abnormalities of the heart

Research output: Contribution to journalJournal articleResearchpeer-review

  1. The usefulness of a trauma probability of survival model for forensic life-threatening danger assessments

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Differences in investigations of sudden unexpected deaths in young people in a nationwide setting

    Research output: Contribution to journalJournal articleResearchpeer-review

  1. Long-term prognosis following hospitalization for acute myocarditis - a matched nationwide cohort study

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Dabigatran and The Risk of Staphylococcus Aureus Bacteremia- A Nationwide Cohort Study

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Mid-regional pro-atrial natriuretic peptide levels before and after hemodialysis predict long-term prognosis

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. Danish Citizen´s Preferences for at-home Oropharyngeal/nasal SARS-CoV-2 Specimen Collection

    Research output: Contribution to journalJournal articleResearchpeer-review

  5. Cardiac Involvement in Women With Pathogenic Dystrophin Gene Variants

    Research output: Contribution to journalJournal articleResearchpeer-review

  • C L Hertz
  • S L Christiansen
  • L Ferrero-Miliani
  • M Dahl
  • P E Weeke
  • G L Ottesen
  • R Frank-Hansen
  • H Bundgaard
  • N Morling
View graph of relations

BACKGROUND: In sudden, unexpected, non-traumatic death in young individuals, structural abnormalities of the heart are frequently identified at autopsy. However, the findings may be unspecific and cause of death may remain unclear. A significant proportion of these cases are most likely caused by inherited cardiac diseases, and the cases are categorized as sudden cardiac death (SCD). The purpose of this study was to explore the added diagnostic value of genetic testing by next-generation sequencing (NGS) of a broad gene panel, as a supplement to the traditional forensic investigation in cases with non-diagnostic structural abnormalities of the heart.

METHODS AND RESULTS: We screened 72 suspected SCD cases (<50 years) using the HaloPlex Target Enrichment System (Agilent) and NGS (Illumina MiSeq) for 100 genes previously associated with inherited cardiomyopathies and channelopathies. Fifty-two cases had non-diagnostic structural cardiac abnormalities and 20 cases, diagnosed with a cardiomyopathy post-mortem (ARVC = 14, HCM = 6), served as comparators. Fifteen (29%) of the deceased individuals with non-diagnostic findings had variants with likely functional effects based on conservation, computational prediction, allele-frequency and supportive literature. The corresponding frequency in deceased individuals with cardiomyopathies was 35% (p = 0.8).

CONCLUSION: The broad genetic screening revealed variants with likely functional effects at similar high rates, i.e. in 29 and 35% of the suspected SCD cases with non-diagnostic and diagnostic cardiac abnormalities, respectively. Although the interpretation of broad NGS screening is challenging, it can support the forensic investigation and help the cardiologist's decision to offer counselling and clinical evaluation to relatives of young SCD victims.

Original languageEnglish
JournalInternational Journal of Legal Medicine (Print)
Volume130
Issue number1
Pages (from-to)91-102
Number of pages12
ISSN0937-9827
DOIs
Publication statusPublished - Jan 2016

    Research areas

  • Adult, Arrhythmogenic Right Ventricular Dysplasia, Cardiomyopathy, Hypertrophic, Death, Sudden, Cardiac, Female, Fibrosis, Forensic Genetics, Forensic Pathology, Genetic Testing, High-Throughput Nucleotide Sequencing, Humans, Hypertrophy, Hypertrophy, Left Ventricular, Hypertrophy, Right Ventricular, Male, Myocardium, Young Adult, Journal Article

ID: 49191944